Widespread Genotype-Phenotype Correlations in Intellectual Disability

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Casanova, M., Gerstner, Z., Sharp, J. L., Casanova, M. F., & Feltus, F. A. (2018). Widespread Genotype-Phenotype Correlations in Intellectual Disability. Frontiers in Psychiatry, 9, 535-535. https://doi.org/10.3389/fpsyt.2018.00535

Publication date: 29 Oct 2018 Added to AutiHub: 14 Sep 2026 Type: Article Article language: English
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Authors

Publication authors
5
Publication authors identified as autistic
1 / 5 (20.0%)
  1. Manuel Casanova *
  2. Zachary Gerstner
  3. Julia L. Sharp
  4. Manuel F. Casanova
  5. Frank Alex Feltus

Abstract

Background: Linking genotype to phenotype is a major aim of genetics research, yet the underlying biochemical mechanisms of many complex conditions continue to remain elusive. Recent research provides evidence that relevant gene-phenotype associations are discoverable in the study of intellectual disability (ID). Here we expand on that work, identifying distinctive gene interaction modules with unique enrichment patterns reflective of associated clinical features in ID. Methods: Two hundred twelve forms of monogenic ID were curated according to comorbidities with autism and epilepsy. These groups were further subdivided according to secondary clinical manifestations of complex versus simple facial dysmorphia and neurodegenerative-like features due to their clinical prominence, modest symptom overlap, and probable etiological divergence. An aggregate gene interaction ID network for these phenotype subgroups was discovered via a public database of known gene interactions: protein-protein, genetic, and mRNA coexpression. Additional annotation resources (Gene Ontology, Human Phenotype Ontology, TRANSFAC/JASPAR, and KEGG/WikiPathways) were utilized to assess functional and phenotypic enrichment patterns within subgroups. Results: Phenotypic analysis revealed high rates of complex facial dysmorphia in ID with comorbid autism. In contrast, neurodegenerative-like features were overrepresented in ID with epilepsy. Network analysis subsequently showed that gene groups divided according to clinical features of interest resulted in distinctive interaction clusters, with unique functional enrichments according to gene set. Conclusions: These data suggest that specific comorbid and secondary clinical features in ID are predictive of underlying genotype. In summary, ID form unique clusters, which are comprised of individual conditions with remarkable genotypic and phenotypic overlap.

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Cited references
43
With a DOI
39
Without a DOI, from raw bibliography text
4
2 / 43 (4.7%) cited references include at least one author identified as autistic.
References with data to complete
1 / 43 (2.3%)
References with detected author names
42 / 43 (97.7%)
Without detected author names
1
Without a structured title
0
Without a stable identifier
4
References with raw author names still to review
0
References with external metadata lookup issues
0
These indicators apply to cited references displayed on this page, after technical duplicates have been merged. A reference without a DOI can still support author statistics when a title and author names are available.
Author names detected in the cited bibliography
357
From DOI or external metadata
357
From validated raw bibliography text
0
Raw names already validated
0
Raw names still to review
0
13 / 357 (3.6%) names are linked to an author already present in AutiHub. 344 / 357 (96.4%) names are not yet linked.
Names linked to a person identified as autistic
2 / 357 (0.6%)
Calculated across all author names detected in the cited bibliography. Among names linked to an author already present in AutiHub: 2 / 13 (15.4%). Distinct people identified as autistic: 2 / 349 (0.6%).
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